Association of a common polymorphism in the factor XIII gene with myocardial infarction.
Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G-->T) in exon 2 of the A-subunit gene which codes for an amino acid change three amino acids from the thrombin activation site (Factor XIIIVal34Leu) is a candidate for a role in the pathogenesis of acute myocardial infarction. Factor XIII genotype frequencies were determined in a case-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary artery disease and were evaluated for a history of myocardial infarction. The prevalence of the mutation was lower in patients with myocardial infarction than without (32% vs. 50%), p = 0.0009 and than in controls (32% vs. 48%), p = 0.005. Patients possessing the mutation with a history of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genotype (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patients possessing wild type with MI compared to those without MI. These results indicate that the G-->T mutation coding for factor XIIIVal34Leu is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.
Kohler
H P
HP
Unit of Molecular Vascular Medicine, Leeds General Infirmary, UK.
Stickland
M H
MH
Ossei-Gerning
N
N
Carter
A
A
Mikkola
H
H
Grant
P J
PJ
D016022:Case-Control Studies; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007930:Leucine; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014633:Valine
D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D005176:Factor XIII; D007930:Leucine; D014633:Valine